Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— TOCASU  

Official title:

Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis: An Open Label Randomized Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05112263
• Other study ID #: IEC/2021/000641
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2023
• Est. completion date: June 1, 2026

Study information

• Verified date: March 2023
• Source: Postgraduate Institute of Medical Education and Research
• Contact: Vishal Sharma
• Phone: +917087008099
• Email: docvishalsharma[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomised trial plans to compare oral tofacitinib with intravenous cyclosporine in patients with acute severe ulcerative colitis who have failed to respond to intravenous steroids

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 96
• Est. completion date: June 1, 2026
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

Patients admitted with Acute severe ulcerative colitis as defined by Modified Truelove and Witts Criteria WITH Failure to respond to intravenous steroids (Hydrocortisone 100 mg IV QID OR IV Methylprednisolone 60 mg IV OD) as defined by

• Day 3 non-response as per Oxford criteria (stool frequency of > 8/day, OR stool frequency between 3-8 with CRP > 45 mg/L PLUS

• Ongoing activity as defined by Partial Mayo Score of > 3 (rectal bleeding sub-score of >1)

• Decision to start second line therapy (within 5-7 days of starting intravenous steroids)

Exclusion Criteria:

• Age <18, Age > 65 years

• E1 disease (involvement distal to rectosigmoid junction only)

• Crohn's disease

• Contraindication to intravenous cyclosporine or oral tofacitinib

• Renal failure, uncontrolled hypertension, seizure disorder,and uncorrected hypomagnesemia (<1.5 mg/L)

• Previous thrombosis, or prothrombotic state, on oral contraceptive, history of herpes zoster, active TB, active hepatitis, past opportunistic infections, h/o diverticulitis, Age >50 plus at least one cardiac risk factor

• Patient wants treatment with intravenous infliximab or wants surgery

• Underlying sepsis or active infection (Enteric infections, Clostridium difficile, active hepatitis B or C, Tuberculosis, zoster, CMV disease)

• Toxic megacolon, previous dysplasia or any indication of immediate surgery

• Known malignancy

• Pregnancy or Lactation

• Unwilling to provide consent or for follow-up

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Tofacitinib
For the tofacitinib the dose of 10 mg BD will be administered for 8 weeks (10 mg TDS for initial three days) and then reduced to 5 mg BD for the period of study
• Cyclosporine
: Intravenous Cyclosporine 2 mg/kg continuous infusion for 5-7 days and then shifted to oral cyclosporine 4 mg/kg/day in two divided doses for 12 weeks.Those who respond with intravenous cyclosporine will be shifted to oral cyclosporine 4 mg/kg for 12 weeks while the thiopurine dose is adjusted to the patient's weight

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Postgraduate Institute of Medical Education and Research	All India Institute of Medical Sciences, New Delhi

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment failure	I) At Day 7 Absence of clinical response at day 7 (as defined by Partial Mayo of > 3); II) By Day 98; Relapse (Partial Mayo Score of 3 or more) between day 7 and day 98 requiring additional therapy; Absence of steroid free remission at 14 weeks (Mayo < 2 with MES 1 or less); Need for colectomy, third line medical rescue or biologics or mortality; Serious adverse effect needing interruption of treatment	14 weeks
Secondary	Clinical response	Partial Mayo <4	7 days
Secondary	Absence of steroid free remission	Mayo score of more than 2 with endoscopic sub-score of more than 1	day 98
Secondary	Colectomy free survival	No need for colectomy	98 days
Secondary	Time to clinical response	Partial Mayo of 3 or less	98 days
Secondary	Endoscopic healing	Mayo endoscopic sub-score of 1 or less	Day 98
Secondary	Serious adverse effects	requiring hospitalization, cessation of treatment and events like cardiovascular events, pulmonary embolism, venous thrombosis, any infection, malignancy, gastrointestinal perforation	98 days